Effects of p21Cip1/Waf1 at Both the G1/S and the G2/M Cell Cycle Transitions: pRb Is a Critical Determinant in Blocking DNA Replication and in Preventing Endoreduplication

Niculescu, Alexander B.; Chen, Xinbin; Smeets, Monique; Hengst, Ludger; Prives, Carol; Reed, Steven I.

doi:10.1128/mcb.18.3.1763

Cited by 127 publications

(155 citation statements)

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“…Injection of purified p21 into Xenopus oocytes potently inhibited the G2/M transition and the activating dephosphorylation of cyclin B1/Cdk1 [133]. Ectopic expression of p21 at physiological levels arrested cells at G1/S and G2/M in various mammalian cell lines [134]. This evidence together with the heat-induced expression of these Cdk inhibitors in G1 may suggest the inhibition of Cdk1 activation for a heat-induced G2 block ( fig.…”

Section: Review Articlementioning

confidence: 81%

Heat shock effects on cell cycle progression

Kühl¹,

Rensing²

2000

CMLS, Cell. Mol. Life Sci.

120

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In mammalian cells, short-term (acute) exposure to a moderate heat shock leads to a transient arrest of cells at mainly two cell cycle checkpoints, the G1/S and G2/M transitions. This is documented by the more or less synchronous resumption of cell cycle progression from these checkpoints during recovery. The reason for the accumulation of cells at these checkpoints may be found in activity thresholds of cyclin-dependent kinases (Cdks) at both transitions which are determined by (i) the amounts of the responsible cyclins, (ii) regulatory phosphorylation of the Cdks and (iii) the inhibition of Cdks by associated regulatory proteins (Ckis). All three regulatory systems may be subject to heat-shock-dependent changes, the amounts of Ckis, in particular, being increased. Cdk-dependent phosphorylation of the retinoblastoma protein and the subsequent release of active S-phase-specific transcription factors E2F/DP are considered as major heat-sensitive steps in cell cycle progression. Furthermore, high acute heat shock and long-term (chronic) heat treatment may lead to cell-type-specific forms of cell death. All types of responses to heat treatment are subject to adaptation after a 'priming' treatment, probably due to higher levels of heat shock proteins.

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Section: Review Articlementioning

confidence: 81%

Heat shock effects on cell cycle progression

Kühl¹,

Rensing²

2000

CMLS, Cell. Mol. Life Sci.

120

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“…The loss or deactivation of either cyclin B1 or Cdc2 will block cellular progression out of G2 [46]. The Cip/Kip family proteins including p27 kip1 act as inhibitors of Cdc2 [47,48]. In this study, we showed that although the levels of Cdc2 protein were not changed in the H460 NSCLC cells treated with b-elemene, the levels of phospho-Cdc2 (Thr-161) and cyclin B1 protein were reduced, while the levels of phosphoCdc2 (Tyr-15) and p27 kip1 were increased, all these leading to decreased activity of the Cdc2-cyclin B1 complex.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of β-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death

Wang

Huang

et al. 2005

CMLS, Cell. Mol. Life Sci.

224

161

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Beta-elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of beta-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, beta-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of beta-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.

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“…When transcriptionally upregulated by p53, the p21 WAF1/ CIP1 protein has a decisive role in cell-cycle arrest [49]. Forced expression of p21 can result in G1-, G2- [50], or S-phase arrest [51]. Regulation of G2 by p53 can also be mediated through its ability to downregulate the M-phase promoting factor (MPF), a universal cell-cycle regulatory complex, which consists of two proteins, cyclin B and cdk1 [52].…”

Section: Discussionmentioning

confidence: 99%

Cyclin A1 is a p53-induced gene that mediates apoptosis, G2/ M arrest, and mitotic catastrophe in renal, ovarian, and lung carcinoma cells

Rivera

Mavila

Bayless

et al. 2006

Cell. Mol. Life Sci.

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We were the first to identify cyclin A1 as a p53-induced gene by cDNA expression profiling of p53-sensitive and -resistant tumor cells [Maxwell S. A. and Davis G. E. (2000) Proc. Natl. Acad. Sci. USA 97, 13009-13014]. We show here that cyclin A1 can induce G2 cell cycle arrest, polyploidy, apoptosis, and mitotic catastrophe in H1299 non-small cell lung, TOV-21G ovarian, or 786-0 renal carcinoma cells. More cdk1 protein and kinase activities were observed in cyclin A1-induced cells than in GFP control-induced cells. Thus, cyclin A1 might mediate apoptosis and mitotic catastrophe through an unscheduled or inappropriate activation of cdk1. Two primary renal cell carcinomas expressing mutated p53 exhibited reduced or absent expression of cyclin A1 relative to the corresponding normal tissue. Moreover, renal carcinoma-derived mutant p53s were deficient in inducing cyclin A1 expression in p53-null cells. Cyclin A1 but not cyclin A2 was upregulated in etoposide-treated tumor cells undergoing p53-dependent apoptosis and mitotic catastrophe. Forced upregulation of cyclin A2 did not induce apoptosis. The data implicate cyclin A1 as a downstream player in p53-dependent apoptosis and G2 arrest.

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Effects of p21^Cip1/Waf1 at Both the G₁/S and the G₂/M Cell Cycle Transitions: pRb Is a Critical Determinant in Blocking DNA Replication and in Preventing Endoreduplication

Cited by 127 publications

References 0 publications

Heat shock effects on cell cycle progression

Heat shock effects on cell cycle progression

Antitumor effect of β-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death

Cyclin A1 is a p53-induced gene that mediates apoptosis, G2/ M arrest, and mitotic catastrophe in renal, ovarian, and lung carcinoma cells

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